A meta-analysis of the prevalence of common clinical characteristics in Velocardiofacial syndrome

by Nicotra, Dawn M.

Abstract (Summary)

Background: Velocardiofacial syndrome (VCFS) is a congenital malformation syndrome with an estimated prevalence of 1:4,000 livebirths. Most cases are caused by a common 3 Mb deletion at 22q11.2. This syndrome exhibits wide inter- and intra-familial variability in phenotypic features including physical, developmental, neurological, and neuropsychiatric manifestations despite the general uniformity in deletion size. The purpose of this meta-analysis was to seek explanations for the differences in the reported prevalence rates of various findings; to more accurately estimate the prevalence of each of the nine traits examined; to provide insight into future research; and to improve the ability for genetic counselors and clinicians to provide more appropriate services and offer appropriate resources. Methods: A PubMed search was performed for keywords associated with VCFS. After an exhaustive search, twenty-nine articles were included. Nine traits of interest were chosen along with five predictor variables. From the articles, prevalence data was abstracted, overall prevalence data was calculated, and unweighted and weighted regression analyses were performed. Results: Ascertainment bias may be associated with the prevalence of ADHD; the prevalence of males does not appear to play a role in the discrepant data; the number of years ago a study was published is associated with prevalence of ADHD, cleft palate, palatal findings and VPI; age range is associated with the prevalence of congenital heart defects; having a de novo deletion is significantly associated with the prevalence of cleft palate and SMCP; and geographical location is significantly associated with the prevalence of palatal anomalies. Overall prevalence rates are as follows: ADHD 17.2%, CHD 73.5%, cleft palate 11.6%, submucosal cleft palate 17.0%, velopharyngeal insufficiency 35.1%, any palatal anomaly 54.1%, any psychiatric disorder 34.4%, schizophrenia 12.6%, and hypotonia 64.5%. Conclusions: Due to small sample sizes, it is difficult to draw conclusions on the presented data; however, this analysis provides useful insight into future avenues of research especially with regards to behavioral and psychiatric illnesses. Many findings, especially psychiatric illnesses, associated with VCFS, pose a significant public health burden thus it would be of public health significance to find answers to some of the questions addressed in this study.